The research program involves the biochemical and physiological study of a new polypeptide hormone, epidermal growth factor (EGF) isolated from the submaxillary glands of mice. Mouse EGF is a 53 residue, single chain polypeptide, containing 3 disulfide bonds. The amino acid sequence has been determined. EGF stimulates epidermal proliferation both when administered to newborn animals and in organ culture of chick embryo skin. It also stimulates the growth of corneal epithelium when applied topically to wounded corneas of rabbits, and in corneal organ cultures of chick embryos and human fetuses. Finally, EGF is a potent mitogen for human fibroblasts in culture. The metabolic fate of EGF will be studied using I125-labeled material. The binding of the labeled hormone to the fibroblast membrane and the metabolic consequences of the binding will be examined. We have recently been able to detect the human counterpart of EGF in protein concentrates of human urine. It was assayed by its ability to compete with I125-labeled mouse derived EGF in binding to human fibroblasts. The biological effects of the human EGF are similar to those previously described for the mouse hormone. Our general approach to the problem has been to try to understand the normal role of EGF in the organism, to define its function in cell growth and development, and to understand the biochemical basis for the growth stimulating properties of this new hormone.